Related Experiment Video
Updated: Jul 1, 2025
A Genetic Screen to Isolate Toxoplasma gondii Host-cell Egress Mutants
Published on: February 8, 2012
Toxoplasma sortilin interacts with secretory proteins and it is critical for parasite proliferation
Chenghuan Li1,2, Ning Jiang1,2, Yize Liu1,2
1Key Laboratory of Livestock Infectious Diseases, Ministry of Education, and Key Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Road, Shenyang, 110866, China.
Background:
The human sortilin protein is an important drug target and detection marker for cancer research. The sortilin from Toxoplasma gondii transports proteins associated with the apical organelles of the parasite. In this study, we aimed to determine the intracellular localization and structural domains of T. gondii sortilin, which may mediate protein transportation. Approaches to the functional inhibition of sortilin to establish novel treatments for T. gondii infections were explored.
Methods:
A gene encoding the sortilin protein was identified in the T. gondii genome. Immunoprecipitation and mass spectrometry were performed to identify the protein species transported by T. gondii sortilin. The interaction of each structural domain of sortilin with the transported proteins was investigated using bio-layer interferometry. The binding regions of the transported proteins in sortilin were identified. The effect of the sortilin inhibitor AF38469 on the infectivity of T. gondii was investigated. The binding site of AF38469 on sortilin was determined.
Results:
The subdomains Vps10, sortilin-C, and sortilin-M of the sortilin were identified as the binding regions for intracellular transportation of the target proteins. The sortilin inhibitor AF38469 bound to the Vps10 structural domain of T. gondii sortilin, which inhibited parasite invasion, replication, and intracellular growth in vitro and was therapeutic in mice infected with T. gondii.
Conclusion:
The Vps10, sortilin-C, and sortilin-M subdomains of T. gondii sortilin were identified as functional regions for intracellular protein transport. The binding region for the sortilin inhibitor AF38469 was also identified as the Vps10 subdomain. This study establishes sortilin as a promising drug target against T. gondii and provides a valuable reference for the development of anti-T. gondii drug-target studies.
Insights
Toxoplasma gondii sortilin protein
Area of Science:
- Parasitology
- Molecular Biology
- Drug Discovery
Background:
- Human sortilin is a key target in cancer research.
- Toxoplasma gondii sortilin facilitates protein transport to parasite apical organelles.
- Understanding T. gondii sortilin is crucial for developing new anti-parasitic treatments.
Purpose of the Study:
- To determine the intracellular localization and structural domains of T. gondii sortilin.
- To explore functional inhibition of sortilin for novel T. gondii treatments.
Main Methods:
- Gene identification and immunoprecipitation in T. gondii.
- Mass spectrometry to identify transported proteins.
- Bio-layer interferometry to analyze domain interactions and inhibitor binding.
Main Results:
- Identified Vps10, sortilin-C, and sortilin-M as binding regions for protein transport.
- AF38469 inhibitor binds to the Vps10 domain, inhibiting T. gondii.
- AF38469 demonstrated therapeutic effects in a murine T. gondii infection model.
Conclusions:
- T. gondii sortilin's Vps10, sortilin-C, and sortilin-M subdomains are critical for protein transport.
- The Vps10 subdomain is the binding site for the inhibitor AF38469.
- Sortilin is a promising drug target for treating T. gondii infections.
More Related Videos
11:21Forward Genetics Screens Using Macrophages to Identify Toxoplasma gondii Genes Important for Resistance to IFN-γ-Dependent Cell Autonomous Immunity
Published on: March 12, 2015
09:52Genetic Manipulation in Δku80 Strains for Functional Genomic Analysis of Toxoplasma gondii
Published on: July 12, 2013
Related Concept Videos
01:26Fusion of Secretory Vesicles with the Plasma Membrane
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
01:33Overview of Secretory Vesicles
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
01:28Protein Translocation Machinery on the ER Membrane
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
01:19Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...